Process for preparation of o-(2,6-dichloroanilino)phenylacetic acid and novel intermediate for use in preparation of the same

Abstract

Disclosed is a process for the preparation of o-(2,6-dichloroanilino)phenylacetic acid (Diclofenac) or its pharmacologically acceptable acid addition salt, which comprises hydrolyzing an N,N-disubstituted-o-(2,6-dichloroanilino)phenylacetamide derivative with an alkali. Also a novel intermediate for use in the preparation of Diclofenac, that is, an N,N-disubstituted-o-halogenophenylacetamide in which the halogen is iodine or bromine, is disclosed.

What is claimed is: 
     
       1. A process for the preparation of o-(2,6-dichloroanilino)phenylacetic acid or its pharmacologically acceptable acid addition salt, which comprises reacting an N,N-disubstituted-o-halogenophenylacetamide derivative represented by the following general formula (I): ##STR31## wherein R 1  and R 2 , which may be the same or different, stand for a lower alkyl group, or one of R 1  and R 2  stands for a lower alkyl group and the other of R 1  and R 2  stands for a phenyl or benzyl group, or R 1  and R 2  are bonded together to form a heterocyclic ring together with a nitrogen atom and/or an oxygen atom, and X stands for an iodine or bromine atom, with 2,6-dichloroaniline in the presence of a copper catalyst to form an N,N-disubstituted-o-(2,6-dichloroanilino)phenylacetamide represented by the following general formula (II): ##STR32## wherein R 1  and R 2  are as defined above, and hydrolyzing with an alkali.   
     
     
       2. A process for the preparation of N,N-disubstituted-o-(2,6-dichloroanilino)phenylacetamide derivatives represented by the following general formula (II): ##STR33## wherein R 1  and R 2 , which may be the same or different, stand for a lower alkyl group, or one of R 1  and R 2  stands for a lower alkyl group and the other of R 1  and R 2  stands for a phenyl or benzyl group, or R 1  and R 2  are bonded together to form a heterocyclic ring together with a nitrogen atom and/or an oxygen atom, which comprises reacting an N,N-diisubstituted-o-halogenophenylacetamide derivative represented by the following general formula (I): ##STR34## wherein R 1  and R 2  are as defined above, and X stands for an iodine or bromine atom, with 2,6-dichloroanline in the presence of a copper catalyst.